protein C; vitamin K-dependent protein C; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; contains: vitamin K-dependent protein C light chain; vitamin K-dependent protein C heavy chain; activation peptide (PROC)
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Function
- vitamin K-dependent serine protease
- regulates blood coagulation by inactivating factor Va & factor VIIIa in the presence of Ca+2 & phospholipids
- the vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind Ca+2
- iron & 2-oxoglutarate dependent 3-hydroxylation of aspartate & asparagine is (R) stereospecific within EGF domains
- may be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide
- synthesized as a single chain precursor, which is cleaved into a light chain & a heavy chain held together by a disulfide bond
- the molecular complex is then activated by thrombin, which cleaves a tetradecapeptide from the amino end of the heavy chain at the surface of endothelial cells
- activation of protein C is strongly promoted by thrombomodulin
- thrombin/thrombomodulin complex preferentially activates protein C, whereas free thrombin primarily converts fibrinogen to fibrin
- Ca+2 also binds, with stronger affinity to another site, beyond the GLA domain
- this GLA-independent binding site is necessary for the recognition of the thrombin-thrombomodulin complex
- procoagulant inhibitor
Structure
- N-glycosylated & O-glycosylated
- partial (70%) N-glycosylation of Asn- 371 with an atypical N-X-C site produces a higher molecular weight form referred to as protein C-alpha
- the lower molecular weight form, not N- glycosylated at Asn-371, is protein C-beta
- O-glycosylated with core 1 glycan or possibly core 8 glycan
- belongs to the peptidase S1 family
- contains 2 EGF-like domains
- contains 1 Gla (gamma-carboxy-glutamate) domain
- contains 1 peptidase S1 domain
Compartment
Expression
- expressed & secreted by liver
Pathology
- defects in PROC are the cause of protein C deficiency
- autosomal dominant (heterozygous protein C deficiency)
- often develop thromoembolic disease before age 30
- autosomal recessive homoygous protein C deficiency)
- severe neonatal disease to late-onset thrombophilia
- autosomal dominant (heterozygous protein C deficiency)
More general terms
More specific terms
Additional terms
- coagulation cascade
- protein C deficiency
- protein C in plasma (protein C assay)
- protein C inhibitor; plasma serine protease inhibitor; acrosomal serine protease inhibitor; plasminogen activator inhibitor 3; PAI-3; PAI3; PCI; Serpin A5 (SERPINA5, PCI, PLANH3, PROCI)
- protein C, activated
- thrombin; coagulation factor IIa
- thrombomodulin; TM; fetomodulin; CD141 (THBD, THRM)
- vitamin K
Component of
- factor ix/factor vii/factor x/protein c/protein s/prothrombin/prothrombin complex concentrate
- prothrombin complex concentrate (Autoplex-T, Kcentra)
References
- ↑ Baron M, Norman DG, Campbell ID. Protein modules. Trends Biochem Sci. 1991 Jan;16(1):13-7. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2053133
- ↑ Suttie JW. Synthesis of vitamin K-dependent proteins. FASEB J. 1993 Mar;7(5):445-52. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8462786
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ UniProt http://www.uniprot.org/uniprot/P04070.html
- ↑ Wikipedia; Note: protein C entry http://en.wikipedia.org/wiki/protein_C
- ↑ GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/PROC
- ↑ SeattleSNPs http://pga.gs.washington.edu/data/proc/
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5624
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5624
- OMIM: https://mirror.omim.org/entry/176860
- OMIM: https://mirror.omim.org/entry/188050
- OMIM: https://mirror.omim.org/entry/612283
- OMIM: https://mirror.omim.org/entry/612304
- UniProt: http://www.uniprot.org/uniprot/P04070.html